Healthcare-prescribed opioids are a known contributor to the opioid epidemic. Locally, there was an identified opportunity to improve opioid prescribing practices in cardiac surgical patients. The cardiac surgical team sought to standardise prescribing practices in postoperative patients and reduce opioid prescriptions at discharge. The improvement was undertaken at a large midwestern freestanding children’s hospital with over 400 beds and 120 cardiac surgeries annually. A multidisciplinary team was formed, using the model for Improvement to guide the improvement work. The key improvement interventions included standardised evidence-based prescribing guidelines based patient age and surgical approach, enhanced pain management with non-opioid medications, and integration of prescribing guidelines into the electronic health record. The primary outcome measure was rate of compliance with the prescribing guidelines and secondary measures included morphine equivalent dosing at discharge, opioid-free discharge, and length of stay. A balancing measure of opioid re-prescriptions was tracked. There were 289 patients included in the primary study period (January 2019 through December 2021). Sustainability of key outcomes was tracked though December 2022. The guideline compliance increased from 24% to 100%. The morphine equivalent dosing decreased to 22.5 in 2021 then 0 in 2022, from baseline of 36.25 in 2019. Opioid-free discharges decreased from 8% (2019) to 1.5% (2021) and 0% in 2022. Establishment and compliance with standardised guidelines for post-operative cardiac surgical pain management yielded a reduction in morphine equivalent dosing, an increase opioid-free discharges, and no increase in length of stay or opioid re-prescriptions.

This study aimed to assess the impact of hypertensive disorders of pregnancy on infant neurodevelopment by comparing 6-month and 2-year psychomotor development outcomes of infants exposed to gestational hypertension (GH) or preeclampsia (PE) versus normotensive pregnancy (NTP). Participating infants were children of women enrolled in the Postpartum Physiology, Psychology and Paediatric (P4) cohort study who had NTPs, GH or PE. 6-month and 2-year Ages and Stages Questionnaires (ASQ-3) scores were categorised as passes or fails according to domain-specific values. For the 2-year Bayley Scales of Infant and Toddler Development (BSID-III) assessment, scores > 2 standard deviations below the mean in a domain were defined as developmental delay. Infants (n = 369, male = 190) exposed to PE (n = 75) versus GH (n = 20) and NTP (n = 274) were more likely to be born small for gestational age and premature. After adjustment, at 2 years, prematurity status was significantly associated with failing any domain of the ASQ-3 (p = 0.015), and maternal tertiary education with increased cognitive scores on the BSID-III (p = 0.013). However, PE and GH exposure were not associated with clinically significant risks of delayed infant neurodevelopment in this study. Larger, multicentre studies are required to further clarify early childhood neurodevelopmental outcomes following hypertensive pregnancies.

This paper studies the role of central bank communication for the monetary policy transmission mechanism using text analysis techniques. In doing so, we derive sentiment measures from European Central Bank (ECB)’s press conferences indicating a dovish or hawkish tone referring to interest rates, inflation, and unemployment. We provide strong evidence for predictability of our sentiments on interbank interest rates, even after controlling for actual policy rate changes. We also find that our sentiment indicators offer predictive power for professionals’ expectations, the disagreement among them, and their uncertainty regarding future inflation as well as future interest rates. Policy communication shocks identified through sign restrictions based on our sentiment measure also have significant effects on real outcomes. Overall, our findings highlight the importance of the tone of central bank communication for the transmission mechanism of monetary policy, but also indicate the necessity of refinements of the communication policies implemented by the ECB to better anchor inflation expectations at the target level and to reduce uncertainty regarding the future path of monetary policy.

Using the dual-pathway framework (Beach et al., 2022a), we tested a Neuro-immune Network (NIN) hypothesis: i.e., that chronically elevated inflammatory processes may have delayed (i.e., incubation) effects on young adult substance use, leading to negative health outcomes. In a sample of 449 participants in the Family and Community Health Study who were followed from age 10 to age 29, we examined a non-self-report index of young adult elevated alcohol consumption (EAC). By controlling self-reported substance use at the transition to adulthood, we were able to isolate a significant delayed (incubation) effect from childhood exposure to danger to EAC (β = −.157, p = .006), which contributed to significantly worse aging outomes. Indirect effects from danger to aging outcomes via EAC were: GrimAge (IE = .010, [.002, .024]), Cardiac Risk (IE = −.004, [−.011, −.001]), DunedinPACE (IE = .002, [.000, .008]). In exploratory analyses we examined potential sex differences in effects, showing slightly stronger incubation effects for men and slightly stronger effects of EAC on aging outcomes for women. Results support the NIN hypothesis that incubation of immune pathway effects contributes to elevated alcohol consumption in young adulthood, resulting in accelerated aging and elevated cardiac risk outcomes via health behavior.

Globally, glaciers are changing in response to climate warming, with those that terminate in water often undergoing the most rapid change. In Alaska and northwest Canada, proglacial lakes have grown in number and size but their influence on glacier mass loss is unclear. We characterized the rates of retreat and mass loss through frontal ablation of 55 lake-terminating glaciers (>14 000 km2) in the region using annual Landsat imagery from 1984 to 2021. We find a median retreat rate of 60 m a−1 (interquartile range = 35–89 m a−1) over 1984–2018 and a median loss of 0.04 Gt a−1 (0.01–0.15 Gt a−1) mass through frontal ablation over 2009–18. Summed over 2009–18, our study glaciers lost 6.1 Gt a−1 to frontal ablation. Analysis of bed profiles suggest that glaciers terminating in larger lakes and deeper water lose more mass to frontal ablation, and that the glaciers will remain lake-terminating for an average of 74 years (38–177 a). This work suggests that as more proglacial lakes form and as lakes become larger, enhanced frontal ablation could cause higher mass losses, which should be considered when projecting the future of lake-terminating glaciers.

A subfossil robber fly (Diptera: Asilidae) from the genus Lasiopogon Loew is reported from a Beringian rodent, Arctic ground squirrel, Urocitellus parryii Richardson (Rodentia: Sciuridae), midden in the Yukon Territory, Canada, dated to about 16 500 years old. This is the first asilid reported from Quaternary-aged material and represents the first (sub)fossil for this genus and for the subfamily Stichopogoninae.

Objectives/Goals: Kentucky (KY) is a high priority ending the HIV epidemic state, with high rates of new HIV diagnoses tied to injection drug use. The overall goal of this pilot is to launch sentinel surveillance of bloodborne infections and drug compounds among people who inject drugs (PWID) to monitor trends in near-real time and inform rapid community response. Methods/Study Population: In collaboration with the Clark County, KY, syringe service program (SSP), the pilot study involves two 1-month waves of data collection: enrolling eligible SSP participants and conducting anonymous behavioral surveys, collection of participants’ syringes, laboratory testing of syringes to detect HIV and hepatitis C (HCV), drug residue testing through National Institute of Standards and Technology, and statistical modeling approaches to produce outputs of bloodborne infection and drug detection. Syringes are tested from each enrolled individual for: 1) HIV antibody; 2) HCV antibody; 3) HIV and HCV PCR; 4) HIV antigen; and 5) drug residue. Collaboration with community and PWID stakeholders will identify optimal messaging for reporting results. Results/Anticipated Results: The first wave community-facing pilot was conducted in September–October 2024. 29 survey responses were obtained; median age of the sample is 42 years, 55.2% are gender female; 37.9% reported unstable housing in the past week. Primary drugs of injection reported via survey in the prior month were methamphetamine (62.1%), heroin (13.8%), fentanyl (13.8%), buprenorphine (10.3%), meth and fentanyl in combination (3.4%). PWID reported returning 900 used syringes and a median of 15 per participant visit. At most recent testing, 69.0% reported a positive HCV test; 0% reported a positive HIV test. Some level of drug checking with fentanyl test strips in past month was reported by 51.7%. Initially, 20 syringes were tested for drug compounds; results are pending. HIV and HCV detection testing will be completed by early 2025. Discussion/Significance of Impact: Early results document proof of concept for our sentinel surveillance study; all individuals screened were willing to participate in surveys and syringe collection. New methods to identify risk for disease outbreaks and emerging drugs can inform rapid allocation of prevention resources at a community level, especially where testing is infrequent.

Objectives/Goals: Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer (BC) with limited treatment options. Mortality rate is especially high in African American (AA) women of reproductive age. High levels of intracellular calcium (Ca2+) have been shown in TNBC cells. This study is to investigate Ca2+ channel blockers (CCBs) as therapy for TNBC. Methods/Study Population: Two human TNBC cell lines obtained from ATCC – HCC1806, and MDA-MB-453 are treated with CCBs, Cilnidipine (Cil), and Mibefradil (Mib), in a concentration- and time-dependent manner. Cell proliferation assays are performed by the MTS cell viability assay. Intracellular Ca2+ levels are measured using the fluorescent dye: Fluro 4-AM. Apoptosis is determined by flow cytometry using Annexin V staining and mitochondrial permeability will be assessed by the Mito JC-1 assay. Expression of Ca2+ signaling genes will be quantitated by real-time polymerase chain reaction (RT-PCR). Potential pathways of CCB efficacy will be identified by ingenuity pathway analysis (IPA). Results/Anticipated Results: Our findings show both CCBs decrease cell proliferation in a concentration- and time-dependent manner to a maximum of 80% vs. control in both TNBC cells. Flow cytometry findings on both TNBC cells treated with both drugs at 20 µM for 24 hours depicts late apoptosis. Interestingly, Mib did not change the intracellular Ca2+ level in HCC1806 cells yet decreased in MDA-MB-453 cells by fivefold, while Cil increased the intracellular Ca2+ level in both cells almost twofold. It is anticipated that Mito JC-1 assay depict decreased mitochondrial potential in both cells. For reverse transcription polymerase chain reaction, it is anticipated that CCB treatment will increase transient receptor potential Ca2+ channels and decrease voltage-gated Ca2+ channels in both cells. IPA analysis is expected to show apoptotic pathways are involved in TNBC via CCB treatment. Discussion/Significance of Impact: TNBC lacks the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Treatment options for TNBC remain severely limited. Our findings that both Cil and Mib can inhibit proliferation of human breast cancer cell lines indicate repurposing CCBs as treatment for TNBC warrants further investigation.

This paper presents detailed analyses of the Reynolds stresses and their budgets in temporally evolving stratified wakes using direct numerical simulation. Ensemble averaging is employed to mitigate statistical errors in the data, and the results are presented as functions of both the transverse and vertical coordinates – at time instants across the near-wake, non-equilibrium, and quasi-two-dimensional regimes for wakes in weakly and strongly stratified environments. Key findings include the identification of dominant terms in the Reynolds stress transport equations and their spatial structures, the generation and destruction processes of the Reynolds stresses, and the energy transfer between the Reynolds stress and the mean flow. The study also clarifies the effects of the Reynolds number and the Froude number. Additionally, we assess the validity of the eddy-viscosity type models and some existing closures for the Reynolds stress model, highlighting the limitations of isotropy and return-to-isotropy hypotheses in stratified flows.

This article replicates and “stress tests” a recent finding by Eckel and Grossman (2003) that matching subsidies generate substantially higher Charity Receipts than theoretically comparable rebate subsidies. In a first replication treatment, we show that most choices are consist with a “constant (gross) contribution” rule, suggesting that inattention to the subsidies’ differing net consequences may explain the higher revenues elicited with matching subsidies. Results of additional treatments suggest that (a) the charity dimension of the decision problems has little to do with the result, and (b) extra information regarding the net consequences of decisions reduces but does not eliminate the result.

Laboratory experiments are frequently used to examine the nature of individuals’ social and risk preferences and inform economic theory. However, it is unknown whether the preferences of volunteer participants are representative of the population from which the participants are drawn, or whether they differ due to selection bias. To answer this question, we measured the preferences of 1,173 students in a classroom experiment using a trust game and a lottery choice task. Separately, we invited all students to participate in a laboratory experiment using common recruitment procedures. To evaluate whether there is selection bias, we compare the social and risk preferences of students who eventually participated in a laboratory experiment to those who did not, and find that they do not differ significantly. However, we also find that people who sent less in a trust game were more likely to participate in a laboratory experiment, and discuss possible explanations for this behavior.